Impact of allele copy number of polymorphisms in FCGR3A and FCGR3B genes on susceptibility to ulcerative colitis

Kouichi Asano, Takayuki Matsumoto, Junji Umeno, Atsushi Hirano, Motohiro Esaki, Naoya Hosono, Toshiyuki Matsui, Yutaka Kiyohara, Yusuke Nakamura, Michiaki Kubo, Takanari Kitazono

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Polymorphisms in the Fcγ receptor genes have been implicated in several autoimmune diseases, including ulcerative colitis (UC). However, most of these reports had not taken into account the effect of copy number variation at this region. Methods: We investigated the combined effect of allele and gene copy number of FCGR3A-158F/V and FCGR3B-NA1/NA2 on susceptibility to UC. Study subjects were composed of a total of 752 Japanese patients with UC and 2062 Japanese control subjects. To estimate allele copy number of the 2 polymorphisms, we integrated the results of PCR-based real-time Invader assay (PCR-RETINA) that measures the allelic ratio and Taqman assay that detects the total copy number. We analyzed the associations of allele copy number with UC using logistic regression model. Results: Gene and allele copy numbers of FCGR3A and FCGR3B were successfully determined in more than 99.5% of the study subjects. Allele copy number of FCGR3A-158F/V demonstrated significant association with susceptibility to UC (P = 0.02), although each single-nucleotide polymorphism and copy number variation alone did not show significant association. Although allele copy number of FCGR3B-NA1/NA2 (P = 0.002) also showed significant association with UC susceptibility, this association seemed to reflect the effect of FCGR3B gene copy number. Subsequent haplotype analyses revealed a strong association of a haplotype FCGR2A-131H/R and copy number of FCGR3B gene (P = 6.5 × 10-9). Conclusions: Allele copy number of FCGR3A-158F/V and FCGR3B gene copy number were associated with UC susceptibility. Our results suggest that organizing handling of immune complex by FCGR3A, FCGR3B, and FCGR2A may play a crucial role in the pathogenesis of UC.

Original languageEnglish
Pages (from-to)2061-2068
Number of pages8
JournalInflammatory Bowel Diseases
Volume19
Issue number10
DOIs
Publication statusPublished - Sep 1 2013

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DNA Copy Number Variations
Ulcerative Colitis
Alleles
Gene Dosage
Genes
Haplotypes
Logistic Models
Fc Receptors
Antigen-Antibody Complex
Autoimmune Diseases
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Gastroenterology

Cite this

Impact of allele copy number of polymorphisms in FCGR3A and FCGR3B genes on susceptibility to ulcerative colitis. / Asano, Kouichi; Matsumoto, Takayuki; Umeno, Junji; Hirano, Atsushi; Esaki, Motohiro; Hosono, Naoya; Matsui, Toshiyuki; Kiyohara, Yutaka; Nakamura, Yusuke; Kubo, Michiaki; Kitazono, Takanari.

In: Inflammatory Bowel Diseases, Vol. 19, No. 10, 01.09.2013, p. 2061-2068.

Research output: Contribution to journalArticle

Asano, K, Matsumoto, T, Umeno, J, Hirano, A, Esaki, M, Hosono, N, Matsui, T, Kiyohara, Y, Nakamura, Y, Kubo, M & Kitazono, T 2013, 'Impact of allele copy number of polymorphisms in FCGR3A and FCGR3B genes on susceptibility to ulcerative colitis', Inflammatory Bowel Diseases, vol. 19, no. 10, pp. 2061-2068. https://doi.org/10.1097/MIB.0b013e318298118e
Asano, Kouichi ; Matsumoto, Takayuki ; Umeno, Junji ; Hirano, Atsushi ; Esaki, Motohiro ; Hosono, Naoya ; Matsui, Toshiyuki ; Kiyohara, Yutaka ; Nakamura, Yusuke ; Kubo, Michiaki ; Kitazono, Takanari. / Impact of allele copy number of polymorphisms in FCGR3A and FCGR3B genes on susceptibility to ulcerative colitis. In: Inflammatory Bowel Diseases. 2013 ; Vol. 19, No. 10. pp. 2061-2068.
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AU - Matsumoto, Takayuki

AU - Umeno, Junji

AU - Hirano, Atsushi

AU - Esaki, Motohiro

AU - Hosono, Naoya

AU - Matsui, Toshiyuki

AU - Kiyohara, Yutaka

AU - Nakamura, Yusuke

AU - Kubo, Michiaki

AU - Kitazono, Takanari

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AB - Background: Polymorphisms in the Fcγ receptor genes have been implicated in several autoimmune diseases, including ulcerative colitis (UC). However, most of these reports had not taken into account the effect of copy number variation at this region. Methods: We investigated the combined effect of allele and gene copy number of FCGR3A-158F/V and FCGR3B-NA1/NA2 on susceptibility to UC. Study subjects were composed of a total of 752 Japanese patients with UC and 2062 Japanese control subjects. To estimate allele copy number of the 2 polymorphisms, we integrated the results of PCR-based real-time Invader assay (PCR-RETINA) that measures the allelic ratio and Taqman assay that detects the total copy number. We analyzed the associations of allele copy number with UC using logistic regression model. Results: Gene and allele copy numbers of FCGR3A and FCGR3B were successfully determined in more than 99.5% of the study subjects. Allele copy number of FCGR3A-158F/V demonstrated significant association with susceptibility to UC (P = 0.02), although each single-nucleotide polymorphism and copy number variation alone did not show significant association. Although allele copy number of FCGR3B-NA1/NA2 (P = 0.002) also showed significant association with UC susceptibility, this association seemed to reflect the effect of FCGR3B gene copy number. Subsequent haplotype analyses revealed a strong association of a haplotype FCGR2A-131H/R and copy number of FCGR3B gene (P = 6.5 × 10-9). Conclusions: Allele copy number of FCGR3A-158F/V and FCGR3B gene copy number were associated with UC susceptibility. Our results suggest that organizing handling of immune complex by FCGR3A, FCGR3B, and FCGR2A may play a crucial role in the pathogenesis of UC.

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